Cardiac allograft vasculopathy: Insights on pathogenesis and therapy

Abstract

Cardiac allograft vasculopathy (CAV) is a unique accelerated form of coronary vascular disease affecting heart transplant recipients. This complication is a significant contributor to medium‐ to long‐term post‐transplant morbidity and mortality. There is a high prevalence of CAV with approximately one in three patients developing CAV by 5 years post‐transplant. Morphologically, CAV is characterized by concentric coronary intimal hyperplasia in both the epicardial arteries and intramural microvasculature. Although several immune and non‐immune factors have been identified, their precise pathogenic mechanisms, interactions, and relative importance in the development of CAV are not well defined. The advent of improved imaging surveillance modalities has resulted in earlier detection during the disease process. However, overall management of CAV remains challenging due to paucity of treatment. This review aims to discuss key concepts on the pathogenesis of CAV and current management strategies, focusing on the use of mammalian target of rapamycin inhibitors.

Allograft or Recipient ST2 Deficiency Oppositely Affected Cardiac Allograft Vasculopathy via Differentially Altering Immune Cells Infiltration

“…While great improvement has been achieved in the precaution of acute rejection, CAV is still primarily resistant to therapy. The immunopathology of CAV is not well understood ( 18 ). The aim of this study was to accurately address the role of IL-33/ST2 signaling in cardiac allograft vasculopathy via deleting ST2 in allograft or recipient respectively.…”

Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De‐novo heart transplant recipients: Design of the randomized controlled EVOLVD trial

“…However, the relative contribution of traditional atherosclerosis to the development of CAV is contested. Cardiac allograft vasculopathy seems in part to be caused by immunological mechanisms, 1 and antibody‐mediated rejection is associated with an increased risk of CAV. In the SCHEDULE trial, we showed that an early switch from a calcineurin‐based immunosuppressive regimen to a drug combination based on everolimus ameliorated the increase in the allograft coronary artery intima thickness in de novo heart transplant recipients 18 .…”

“…The longevity of cardiac allografts is limited by cardiac allograft vasculopathy (CAV). This is a unique form of accelerated atherosclerosis that is characterized by a diffuse, progressive thickening of the arterial intima throughout the graft and loss of the microvasculature 1 . Cardiac allograft vasculopathy is present in 48% of heart transplant recipients within 10 years after transplantation and accounts for 30% of deaths occurring beyond the first year 2 .…”

Diagnostic Intravascular Imaging Modalities for Cardiac Allograft Vasculopathy

“…Donor-related factors such as older age, donorderived coronary artery disease, higher body mass index, hypertension, diabetes mellitus, cigarette use are associated with increased risks of CAV [8][9][10]. Physiologic changes at the donor caused by brain death can trigger the production of proinflammatory cytokines leading to the endothelial injury [11,12]. Systemic activation of matrix metalloproteinases in donors with intracerebral hemorrhage can contribute to the migration of smooth muscle cells from the coronary media into the intima [13].…”